1988
Discovery of the LDL receptor-related protein (LRP). One of the
largest membrane proteins to date, LRP was found using a homology
screening approach against the most conserved sequences in the LDL
receptor ligand binding domain. Because of its striking structural
similarity to the LDL receptor, in particular the presence of 4
highly conserved ligand binding domains, LRP was proposed to function
as a hypothetical chylomicron remnant receptor that, in concert
with the LDL receptor, was thought to mediate the removal of dietary
cholesterol by the liver.

1994
Gene transfer of an endogenous inhibitor of ligand binding to
LRP using recombinant adenovirus results in the accumulation of
remnant lipoproteins in the circulation of LDL receptor knockout
mice.

1995
Genetic disruption of RAP, a molecular chaperone for LRP, results
in impaired production of LRP and a related receptor, megalin

1996
Genetic disruption of the LDL receptor family member megalin causes
holoprosencephaly, a frequent genetic malformation of human newborns.

1998
Definitive evidence for a function of LRP as a chylomicron remnant
receptor was obtained in genetically altered mice in which LRP
could be conditionally inactivated in the liver.

1998
A class of cytoplasmic adaptor proteins containing PTB protein
interaction domains is shown to interact with the cytoplasmic
tail of LDL receptor family members and the amyloid precursor
protein.